syn-Selective Epoxidation of Chiral Terminal Allylic Alcohols with a Titanium Salalen Catalyst and Hydrogen Peroxide

In the Sharpless asymmetric epoxidation of chiral secondary allylic alcohols, one substrate enantiomer is predominantly converted to the anti-epoxy alcohol. We herein report the first highly syn-selective epoxidation of terminal allylic alcohols using a titanium salalen complex as catalyst, at room temperature, and aqueous hydrogen peroxide as oxidant. With enantiopure terminal allylic alcohols as substrates, the epoxy alcohols were obtained with up to 98 % yield and up to >99 : 1 dr (syn). Catalyst loadings as low as 1 mol % can be applied without eroding the syn-diastereoselectivity. Modification of the allylic alcohol to an ether does not affect the diastereoselectivity either [>99 : 1 dr (syn)]. Inverting the catalyst configuration leads to the anti-product, albeit at lower dr (ca. 20 : 1). The synthetic potential is demonstrated by a short, gram-scale preparation of a tetrahydrofuran building block with three stereocenters, involving two titanium salalen catalyzed epoxidation steps.